Carotid Surgery versus Endovascular
Approach
*
Enrico Giuliani,1Susanna Genedani,2Roberto Moratto,3Jessica Veronesi,3Chiara Carone,2 Cinzia Bonvecchio,1Francesco Mosca,1Gioachino Coppi,3and Alberto Barbieri,1Modena, Italy
Background: Carotid endarterectomy (CEA) is the gold standard for treating severe carotid ar-tery stenosis, whereas carotid arar-tery stenting (CAS) represents an endovascular alternative. The objective of this study was to assess the potential neural damage following open or endovascu-lar carotid surgery measured by peripheral blood concentration of 3 biomarkers: S100b, matrix metalloproteinase-9 (MMP-9), andD-dimer.
Methods: Data for this prospective investigation were obtained from the Carotid Markers study (January 2010e2011), which sought to measure the levels of specific biomarkers of neuronal damage and thrombosis on candidates to CEA or CAS presenting at the Department of Vascular Surgery of the Nuovo Ospedale S. Agostino Estense of Modena (Italy) at baseline and at 24 hr after surgery. Relevant medical comorbidities were noted.
Results: A total of 113 consecutive patients were enrolled in the study, 41 in the endarterec-tomy group and 72 in the endovascular group. The baseline levels of the studied biomarkers did not show any statistically significant difference between the groups with the exception of MMP-9, which showed higher concentrations in the endovascular group (median 731 vs. 401, P ¼ 0.0007), while 24 hr after surgery the endarterectomy group featured significantly higher pe-ripheral blood concentrations of MMP-9, S100b, andD-dimer. Conversely, no significant
differ-ence was detected in the endovascular group except theD-dimer level.
Conclusions: Neural damage biomarkers demonstrated a substantial difference between open and endovascular carotid surgery, which, if performed in selected patients, may become a less invasive alternative to CEA.
INTRODUCTION
Stroke is one of the leading causes of death and per-manent disability in high-income countries.1 Signif-icant carotid artery stenosis may be a predisposing factor in stroke, so surgical treatment can reduce
the risk of recurrent stroke in patients with severe carotid stenosis.2
Carotid endarterectomy (CEA) is the gold stan-dard for treating severe carotid artery stenosis, whereas carotid artery stenting (CAS) represents its endovascular alternative.3,4 Open surgery has
*This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/3.0/).
The study was funded with institutional funds for independent research of the University of Modena and Reggio Emilia.
Disclosures: Prof. Gioachino Coppi is the patent holder of Mo.MaÒ and Piton GCÒ. Dr. Roberto Moratto and Dr. Jessica Veronesi work at the Department of Vascular Surgery of the Nuovo Ospedale S. Agos-tino Estense Modena, Italy under the direction of prof. Gioachino Coppi.
1School of Anesthesia and Intensive Care, University of Modena and
Reggio Emilia, Modena, Italy.
2
Deparment of Pharmacology, University of Modena and Reggio Emilia, Modena, Italy.
3Department of Vascular Surgery, Nuovo Ospedale S. Agostino
Estense, University of Modena and Reggio Emilia, Modena, Italy. Correspondence to: Alberto Barbieri, Policlinico, via del Pozzo 71, Modena 41124, Italy; E-mail:alberto.barbieri@unimore.it
Ann Vasc Surg 2014; 28: 1671–1679 http://dx.doi.org/10.1016/j.avsg.2014.05.006
Ó 2014 The Authors. Published by Elsevier Inc. All rights reserved. Manuscript received: December 22, 2013; manuscript accepted: May 30, 2014; published online: June 6, 2014.
demonstrated, on one hand, a lower periprocedural risk of death and stroke, with, on the other hand, a higher risk of acute myocardial infarction (AMI) and cranial nerve injury, making percutaneous transluminal angioplasty and CAS second-line treatment options for carotid artery stenosis. How-ever, no long-term differences concerning the outcome of stroke or death were demonstrated in the meta-analysis by Meier et al.5
This meta-analysis and several trials, Carotid Revascularization Endarterectomy versus Stenting Trial (CREST),6,7 Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS),8and Steant-Protected Angioplasty versus Carotid Endar-terectomy (SPACE),9 have shifted the balance in favor of CEA,10because of the lower incidence of ce-rebrovascular complications,11 reserving endovas-cular techniques to selected cases.
The diagnosis of periprocedural stroke relies on clinical parameters and neuroimaging tech-niques,12 as with all other forms of acute stroke. Similarly to what has been done for early triage and evaluation of cardiac symptoms compatible with AMI, various panels of biomarkers of neural damage13e15 have been developed and validated in recent years. The necessity of adopting a multiple markers approach is based on the absence of a single molecule capable of identifying brain damage in all its forms. S100b,16
a calcium-binding protein, is released from astrocytesda cellular population that is vital to neuronal trophic support being involved in most repair and apoptosis processes. Ma-trix metalloproteinase-9 (MMP-9),17,18a gelatinase, is less neuron specific as it is a marker of inflamma-tion, present in both active and inactive forms, the former being more abundant within the bloode brain barrier indicating, at high concentration, dam-age at this level.D-dimer19is the end product of
fibri-nolytic process. These 3 markers are part of the triage stroke panel,13the brain natriuretic peptide, present in the original version, was excluded from the perioperative assays as it could be biased by surgery-related variables not correlated to neural damage, such as fluid therapy and cardiac function. A biomarker-based approach can be proposed to assess potential periprocedural neurological damage whose effects are still present at 24 hr; this could help to identify more subtle variations and uncover subclinical, active injuries that might contribute to the development of long-term effects. In fact, an acute elevation of these biomarkers could result solely from minor surgical alterations to cerebral perfusion and inflammation, while a lasting eleva-tion at 24 hr may be correlated to a more substantial lesion.
The main objective of this investigation was to assess the potential neural damage following open versus endovascular carotid surgery measured by pe-ripheral blood concentration of 3 biomarkers (S100b, MMP-9,D-dimer) at baseline and 24 hr after surgery.
METHODS
Data for this prospective pilot investigation were ob-tained from the Carotid Markers (CARMA) study (January 2010e2011), which sought to measure the levels of specific biomarkers of neuronal damage and thrombosis on candidates to CEA or CAS pre-senting at the Department of Vascular Surgery of the Nuovo Ospedale S. Agostino Estense (Baggio-vara, Modena, Italy) at baseline and at 24 hr after surgery. Approval from Institutional Ethics Com-mittee of Modena was obtained before study initia-tion. Patients were included in the analysis if CEA or CAS were performed according to the below described techniques. Written formal consent was obtained from the study participants or legal desig-nate. Demographic, clinical, laboratory, and radio-graphic data were collected by a standardized protocol. The American Society of Anesthesiologists (ASA) physical status classification system was adopted as a measure of the overall physical health of the patient before surgery.
Initial assessment of the patient was performed by echo-color duplex scan and angio-computed to-mography (CT) of the neck and brain to define the anatomical characteristics of the aortic arch, supra-aortic vessels, and intracranial circulation. Asymp-tomatic patients with stenosis >80% and/or ulcerated lesions >50% and symptomatic patients with stenosis >60% and/or ulcerated lesions >50% were considered for treatment. Patients over 65 years of age were primarily considered for CAS at this center when favorable anatomies were documented at angio-CT studies. Suitable anatomic criteria for CAS included bovine and normal arches (type I, II, and III) and adequate femoral artery ac-cess. Endovascular treatment was withhold in cases of stenosis of the brachiocephalic artery or at the origin of the left common carotid artery (CCA) and calcification of the aortic arch. Patients were consid-ered for CAS when unsuitable for traditional sur-gery because of clinically significant cardiac disease, severe pulmonary disease, contralateral laryngeal nerve palsy, restenosis>80% after CEA, previous neck radiation exposure or radical neck surgery, and high carotid bifurcation or intracranial extension of a carotid lesion. Finally, CAS was per-formed in patients at high risk of cerebral ischemia during carotid clamping (i.e., occlusion of the
contralateral internal carotid artery (ICA) and anomalies of the circle of Willis). There is no maximum age threshold at this center, but patients aged under 65 years, who were suitable for surgery, were preferably treated with CEA.
All new neurological deficits, defined as previ-ously not documented focal or general neurological signs or symptoms presented by the patient during and after surgery were recorded by a consultant neurologist.
Surgical Techniques
Carotid endarterectomy. The eversion CEA tech-nique was performed through an oblique transection of the ICA from the CCA, endarterectomy by ever-sion of the ICA, endarterectomy of the carotid bifur-cation and of the external carotid artery (ECA), and reimplantation of the ICA on the CCA. Conventional CEA was performed through a longitudinal arterio-tomy from the CCA bifurcation to the ICA on the anterior surface of the artery. Endarterectomy was carried out after careful identification of the cleavage plane. Arteriotomy was routinely closed with a prosthetic patch (Finesse Fine, Maquet, NJ).
The procedure was performed during conscious sedation: after the cannulation of a peripheral vein with a large bore catheter and radial artery with a 20G catheter for invasive monitoring of blood pres-sure, general anesthesia was induced using propofol 1% (1e1.5 mg/kg) and remifentanil continuous infusion at a rate of 0.1e0.15 mg/kg/min. All patients received succinylcholine 1 mg/kg before laryngos-copy and topical lidocaine 4% on the vocal cords before intubation. After the endotracheal tube was positioned, mechanical ventilation started. The su-perficial cervical plexus block was performed using ropivacaine 0.75% (0.8e1.2 mg/kg). Under remi-fentanil continuous infusion at a rate of 0.1mg/kg/ min, the patient regained consciousness with the ability to tolerate orotracheal intubation and me-chanically assisted ventilation; no other anesthetic agent was administered alongside remifentanil. Ce-rebral blood flow adequacy, after carotid clamping, was measured by monitoring the ability of the pa-tient to execute simple orders (squeeze test) issued by the anesthesiologist at regular intervals, of at least 5 min or more frequently if necessary, with the hem-isoma contralateral to the surgical site: inability to perform this task, in the absence of other possible causes such as systemic hypotension, was the indica-tion for carotid shunt placement.
The remifentanil infusion was gradually reduced and completely discontinued at the end of the pro-cedure and the patient was extubated.
The anesthesia protocol used combines a regional technique with conscious sedation to ensure adequate pain control and safe airway management.
Carotid artery stenting. An access was obtained by percutaneous puncture of the common femoral ar-tery under local anesthesia with mepivacaine 5 mg/kg. The Piton GCÒ carotid guide catheter (Medtronic Invatec, Frauenfeld, Switzerland) and Mo.MaÒ,20,21 a proximal cerebral embolic protec-tion device, (Medtronic Invatec) were used in all cases. Predilation was selectively performed with a noncompliant coronary balloon (2.5e3.5 mm in diameter) in case of preocclusive calcified stenosis (a stenosis of at least 90%) which impeded stent deployment. Self-expanding nitinol stents were used in the study. The diameter of the stent was cho-sen according to a 1e2 mm oversizing with a length of 30 or 40 mm. In the case of lesions longer than 40 mm, 2 stents were inserted, with an overlapping of 2e5 mm. Double stenting was employed for longer lesions and not for stent design reinforce-ment (in 1 case double stenting was employed to avoid plaque prolapse). Stents used in this study include X-actÒ (Abbott Vascular, Redwood City, CA), ViVEXXÒ(C. R. Bard, Murray Hill, NJ), Vascu-FlexÒ(B. Braun Medical, Boulogne Cedex, France), and Cristallo Ideale Carotid Stent SystemÒ (Med-tronic Invatec). Postdilation was performed with a
5 20 mm noncompliant balloon (range 4e
5.5 mm) at 8 atm, with inflation and deflation per-formed slowly (1 atm/2 sec). After the final aspira-tion, when there were no signs of clamping intolerance, endovascular flushing to the ECA was performed. Before the removal of the protection de-vice, the postdilation balloon was reintroduced into the ICA and reinflating at a low pressure (4 atm) to further remodel the debris or detached protruding plaque. The balloons in the ECA and CCA were then deflated, allowing passage of the reinstated hematic current into the ECA for 5e10 sec (cerebral flow is blocked by the inflated postdilation balloon). Then balloons were reinflated and the postdilation balloon was deflated and removed. A second aspira-tion was performed, checking for the absence of debris before reinstating blood flow and removing the device. This procedure was intended to mobilize the unstable protruding plaque while the cerebral flow was still blocked and redirect it into the ECA, achieving a spreading effect of any protruding pla-que. An intra- and extracranial angiography post intervention was performed to assess stent patency and eventual residual stenosis (20% is accepted)
and to visualize and assess any potential intracranial embolization.
The choice of the stent used was based on both anatomical and plaque-related criteria: closed cells were preferred in linear vessels with soft plaques, open cells in cases of tortuous anatomies with calci-fied plaques, while hybrid cells were used in soft plaques.
Postoperative Medical Therapy
All candidates to CAS received aspirin 100 mg and clopidogrel 75 mg daily for the 3 days preceding the operation. During both procedures a standard dose of heparin was administered and from the first postoperative day an antiplatelet regimen with aspirin 100 mg, associated for 30 days to clopidogrel in case of CAS. Statins were added as plaque stabi-lizers, when not absolutely contraindicated.
Immunoassays
Blood samples were obtained at admission to the Department of Vascular Surgery and after 24 hr by either venous puncture or a catheter placed in the radial artery for the invasive monitoring of blood pressure. Plasma samples were collected in ethylenediaminetetraacetic acid tubes forD-dimer;
serum samples were collected for S100b and MMP-9 detection. Blood samples were centrifuged at 1,500 g within 60 min from collection. Each serum or plasma sample was subdivided into 2 Cryo-VialsÔ and stored at 80C.
Serum MMP-9 was quantified by a commercially available MMP-9 (human) ELISA kit (DRG Diagnos-tics, DRG Instruments GmbH, Marburg, Germany). Serum S100b was quantified with appropriate fully automated electrochemiluminescence immuno-assay (Cobas; Roche Diagnostics GmbH, Mannheim, Germany) in accordance with the manufacturer’s instructions. Plasma D-dimer concentration was
measured using a fully automated Tina-quant
D-dimer D-DI2 test (Cobas; Roche Diagnostics
GmbH) according to the manufacturer’s instruc-tions. The lower limit of sensitivity of the MMP-9 assay was 0.05 ng/mL, while the analytic range for
D-dimer and S100b was 150e9,000 ng/mL and
0.005e39 mg/L, respectively. Follow-up
All included patients were scheduled for follow-up 1 week after the procedure, 1 and 6 months after-wards: on these occasions a carotid ultrasound scan was acquired by a vascular surgeon, who also evaluated potential surgical complications, while a neurologist performed a detailed neurological
examination to detect potential lesions correlated to surgery and follow their evolution.
Statistical Analysis
Statistical analysis was performed using Stata 10.0 (StataCorp, College Station, TX). Descriptive statis-tics, including median and interquartile range, were obtained for demographic variables, Wil-coxon rank-sum test was used to compare the dis-tributions of continuous variables, the Wilcoxon sign-rank test for paired data, andc2 test for cate-gorical variables. The Spearman’s rank correlation test was used to assess the relationship between 2 interval variables.
RESULTS
A total of 113 consecutive patients were enrolled in the CARMA study, 41 in the endarterectomy group and 72 in the endovascular group.Figure 1reports the enrollment flowchart: 82.9% of the subjects in the endarterectomy group were treated with patch angioplasty and 17.1% with eversion.
The demographics for the study population did not show statistically significant differences be-tween groups as regard to sex, vascular risk factors, and relevant past medical history, with the excep-tion of age and peripheral artery disease (PAD) (Table I); the median degree of preoperative carotid stenosis, measured by echo-color duplex scan as percentage of lumen reduction in the vessel to be operated, was 75% in both groups (P ¼ 0.1961). No deaths were reported during hospital stay and 2 patients died during the follow-up period (1.6%): one for the complications of a stroke at day 24 in the endovascular group and one after a ce-rebral hemorrhage at day 150 in the endarterectomy group.
The mean duration of the perioperative period of the endarterectomy group was 95.8 ± 9.0 min, while for CAS it lasted on average 52.7 ± 17.6 min (P< 0.0001). There were 1 ASA 1, 25 ASA 2, and 15 ASA 3 patients in the endarterectomy group compared with 25 ASA 2, 45 ASA 3, and 2 ASA 4 patients in the endovascular group; the anesthesio-logic and surgical characteristic of the studied cohort presented statistically significant differences of ASA classification and duration of carotid flow arrest, while the proportion of episodes of new neurological deficits during surgery measured as inability to perform squeeze test did not reach the level of significance (Table II). One stroke was re-ported during postoperative period in each group with documented ischemic lesions at brain imaging
and permanent sensory and motor deficit at one hemisoma.
Table IIIsummarizes the complications related to surgery identified during the follow-up; no statisti-cally significant differences of prevalence were pre-sent between the 2 groups.
The baseline levels of the studied biomarkers did not show any statistically significant difference be-tween groups with the exception of MMP-9, which showed higher concentrations in the endovascular group (median 731 vs. 401, P¼ 0.0007). Postopera-tive levels of MMP-9, S100b, and D-dimer were
significantly higher in the endarterectomy group.
D-dimer was the only marker to be higher after
sur-gery in the endovascular group. This profile is compatible with a profile of increased inflammation and astrocyte damage in the endarterectomy group (Fig. 2).
A Wilcoxon rank-sum test was performed to assess the differences in concentration of the studied biomarkers in the individuals who failed the Fig. 1. Enrollment flowchart.
Table I. Patient demographics for endarterectomy and endovascular groups
Demographics Endarterectomy (n¼ 41) Endovascular (n¼ 72) P value Age (years) 71.0 ± 1.3 75.5 ± 0.9 0.0047 Sex (male) 70.7% 59.7% 0.242 Tobacco smoke 24.4% 18.1% 0.421 Dyslipidemia 56.1% 43.1% 0.182 Diabetes 17.1% 27.8% 0.199 Hypertension 70.7% 81.9% 0.167 AMI 14.6% 25.0% 0.195 TIA 19.5% 16.7% 0.703 Stroke 34.1% 20.8% 0.119 PAD 14.6% 36.1% 0.015
TIA, transitory ischemic attack.
Age is expressed as mean ± standard deviation; for the categorical variables, percentages are given as a proportion of the patients who had the characteristics.
Table II. Surgical characteristics of the studied cohort
Endarterectomy (n¼ 41)
Endovascular
(n¼ 72) P value
ASA 2 (2e3) 3 (2e3) 0.0038
Clamp (min) 41.5 (29.5e50) 7.5 (5e10) <0.0001 Squeeze test
failure (%)
21.9% 12.5% 0.158
ASA and clamp are expressed as median and interquartile range; for the categorical variables, percentages are given as a proportion of the patients who had the characteristics. There were 1 ASA 1, 25 ASA 2, and 15 ASA 3 patients in the endarterectomy group compared with 25 ASA 2, 45 ASA 3, and 2 ASA 4 patients in the endovascular group. Seven of the 9 patients who failed to perform the squeeze test in the endarterectomy group were used a shunt to partially restore carotid blood flow. The differences of the distributions of the continuous variables were assessed by the Wilcoxon’s rank-sum test, while for the categorical variablesc2test was used.
Clamp, duration of carotid flow arrest; squeeze test failure, percentage of patients who failed the squeeze test.
squeeze test within each group: there was a statisti-cally significant difference between D-dimer
post-operative levels in the endarterectomy group (median in failure subgroup 1886 vs. 818 ng/mL, P¼ 0.0304). Similarly, a statistically significant dif-ference was shown between postoperative S100b levels in those subjects where shunt was used dur-ing endarterectomy (0.083mg/mL in the shunt sub-group vs. 0.055mg/mL, P ¼ 0.0066).
The Spearman’s rank correlation test was used to assess the relationship between the level of the stud-ied biomarkers at 24 hr and the duration of carotid flow arrest: no statistically significant correlations were observed between the concentrations of the 3 biomarkers included in this panel at 24 hr and the duration of carotid flow arrest.
DISCUSSION
Carotid surgery is one of the main vascular inter-ventions. CEA is considered the gold standard tech-nique for symptomatic stenosis, while CAS is indicated only for selected cases as its generalized application is controversial.3,4In fact, randomized trials have demonstrated an excess in complications for the endovascular treatment when compared with open surgery.10,11 Paraskevas et al.22 in the critics to the CREST study have shown a substantial superiority of CEA versus CAS, but in their conclu-sions they emphasized that CREST used outdated technology and indications. Under this perspective, this study investigates the effects of the implementa-tion of new technical soluimplementa-tions to CAS from a bio-marker’s point of view.
However, the CAS is characterized by shorter duration of the procedure and the potential for reduced invasivity. Factors that may influence the outcome of CAS are the experience of the operator and the anatomical and clinical characteristics of
the patient, which make them suitable for an endo-vascular approach: randomization may be especially challenging because standard evaluation methods (angiography and echocolordoppler) could fail to identify conditions that contraindicate CEA or CAS. Epiaortic vessels angio-CT with analysis of the Willis circle, carotid plaque composition are often necessary to identify patient suitable for CAS. The adoption of specific devices (guide cathe-ters and cerebral protection devices) makes CAS a feasible approach also in patients over 65 years of age, reducing some of the most common complica-tions23e25CAS still remains a technique for selected cases26 but a careful preoperative assessment can extend its application to larger portion of patients, who may benefit from the reduced invasivity and duration of an endovascular approach when compared with open surgery.
The rate of reported complications seems compa-rable between groups, especially when considering the endovascular procedures.11
Mantese et al.6 showed that age was the only parameter affecting treatment efficacy in CAS versus CEA for carotid surgery but the adoption of additional cerebral protection devices and specific guidewires may improve the efficacy of CAS in pa-tients over 70 as suggested current data. In fact con-trary to what are the actual indications to CAS, the present endovascular group was characterized by older age and a higher prevalence of PAD, as a less invasive approach was preferred in higher comor-bidity patients with suitable anatomy, as reflected also by the ASA physical status classification assess-ment. The shorter duration of the procedure, the feasibility with local anesthesia, so without the need for mechanical ventilation, were considered beneficial factors in the perioperative management of these individuals, as an attempt to reduce the impact on the homeostasis of the elderly vascular patient. In fact, in these subjects complications can Table III. Main complications reported during the follow-up period for each group (no statistically significant difference in the prevalence of complications was present between groups)
Groups
Follow-up
1 week (no. of cases) 1 month (no. of cases) 6 months (no. of cases) Endovascular
(n¼ 72)
Reduction of muscle power of the contralateral upper limb (1) Bleeding with hematoma of puncture site (1)
Death because of ischemic stroke (1)
Death because of sepsis (1)
Endarterectomy (n¼ 41)
Hypoglossal nerve involvement (2) Upper limb palsy with thrombosis of the operated vessel (1)a
Ischemic stroke (1)a Death because of cerebral
hemorrhage (1)
a
be related to factors not directly linked to the surgi-cal procedure.
The studied biomarkers showed a significant in-crease from baseline in the open surgery group, even if this was, apparently, not related to the
duration of carotid flow arrest.D-dimer, which
re-flects the activation of the coagulation cascade, raised in both groups likely as a consequence of ca-rotid atherosclerosis and activation of the fibrino-lytic cascade27during and after surgery.
The correlation between the serum/plasma con-centrations of a panel of specific biomarkers with neural damage has already been demonstrated. Here, we propose that their application to vascular surgery, especially to carotid interventions, can contribute to detect subclinical lesions that may not have direct consequences in the short term but can manifest as neurological status deterioration on a longer term. Postoperative cognitive impair-ment is associated to carotid surgery because of possible emboli that may detach from the carotid plaque during the procedure and the underlying clinical condition of the patient that may predispose him to the development of cerebrovascular pathologies.
S100b peripheral levels, although characterized by a half-life of 25 min, have shown a good correla-tion with cerebral lesions 24 hr after cardiac sur-gery28; elevated levels of this protein have been described after CEA probably as consequence of transitory episodes of cerebral hypoperfusion29 and carotid clamping.30Contrary to what reported by Brightwell et al.,29our data show that the treat-ment modality affected S100b peripheral levels 24 hr after the operation only in the CEA group. These findings were not related to the length of the carotid flow arrest, so they may be dependent on a more effective proximal cerebral protection strategy, which, however, calls for further assessment.
MMP-9, a gelatinase, peaks during CEA in corre-lation to vessel occlusion31: it is a marker of inflam-mation and damage of the bloodebrain barrier therefore its postoperative increase could be related to microembolization and/or transient brain tissue damage. Other conditions may influence the con-centration of MMP-9, such as chronic inflammatory diseases, tumors, and venous diseases, but the study compared a preoperative concentration with a post-operative level and it is unlikely that these con-founding conditions are manifested in the 48-hr interval between samples collection.
MMP-9 adds value to the panel of markers as it explores the inflammation and alteration of the bloodebrain barrier that is likely affected during surgery.
Interestingly, in this study, the levels of MMP-9 were significantly higher in the CAS group. This suggests a higher ‘‘baseline’’ inflammatory state or silent areas of damage associated with subclinical Fig. 2. Panel of biomarkers: data regarding S100b
pro-tein, matrix metalloproteinase-9, andD-dimer peripheral
blood levels, at baseline (preoperative) and 24 hr after surgery (postoperative), are reported as median with interquartile range for the endovascular and endarterec-tomy groups.
bloodebrain barrier dysfunction in this group of pa-tients. Nevertheless, the incidence of neurological deficits did not differ in the 2 groups both during surgery and the 6-month follow-up.
The present data show that the endovascular approach determined a minor release of neural damage biomarkers than traditional open surgery for factors independent from carotid flow arrest duration but probably related to intrinsic character-istics of the procedure somehow entailing an improved cerebral protection, as shown by Montorsi et al.21 with a reduced rate of microembolization associated with the use of a proximal protection de-vice. However, the statistically shorter duration of carotid flow arrest experienced during the endovas-cular procedures may have presumably led to a reduced neural damage, as highlighted by the bio-markers’ trend.
The detection of intraprocedural microembolic events with transcranial Doppler could be correlated to the peripheral concentration of the studied biomarkers to provide further validation of this approach.
Limitations
The relatively small group of patients studied, enrolled in a single center, may limit the extent of the conclusions. Randomization was not imple-mented because of the substantially different sur-gical characteristics peculiar to patients suitable for endovascular surgery, which would bias the outcome of the procedures. Even if randomization would have been the best option in statistical terms, the highly individualized diagnostic work-up tailored on the clinical profile of the patients made it incompatible with an investigation on biomarkers.
The panel of markers could have comprised other neuron-specific markers and integrated their levels with imaging data to improve the diagnostic accuracy.
CONCLUSIONS
Peripheral neural damage biomarkers, an auxiliary diagnostic tool in the detection of subclinical lesions, demonstrated a substantial difference between open and endovascular carotid surgery, which, if per-formed in selected patients, may become a less inva-sive alternative to CEA. Data from this study do not support previous literature results obtained in ran-domized trials showing an excess in complications for the endovascular treatment when compared with open surgery. These findings would call for
further investigation to better assess the relationship between open and endovascular surgery and clinical neural damage, both in the acute phase and during follow-up.
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